The DOMUS study protocol: a randomized clinical trial of accelerated transition from oncological treatment to specialized palliative care at home

The Capital Region of Denmark had in 2013 1,735,521 inhabitants with one of the highest incidences (0.6%) and prevalence (4.3%) of cancer in the world as well as a high cancer mortality rate (6.8%). Almost five thousand of the inhabitants of the Capital Region dies of cancer every year (0.25%) [1]. Thus, a substantial need for palliative cancer care is observed.

Studies have shown that most patients with advanced cancer prefer to spend the last part of their life at home (50-90%) [2, 3]. However, in most western countries more than half of the patients with advanced cancer die in hospitals [3‐9]. A recent systematic review by Gomes et al. showed that most people with different terminal diseases preferred to die at home and the majority of patients did not change preferences as their illnesses progressed [10]. Similar preferences were reported in a retrospective Danish survey, which indicated that the majority of cancer patients in the palliative care phase preferred to die in their own home (81%); however, the reported preference for dying at home decreased towards time of death (64%) [11]. Further, a recent prospective Danish study indicated that the majority (71%) of cancer patients in palliative care preferred to die in their own home [12]. According to the National Board of Health, 55% of Danish cancer patients died in hospitals, 18% in nursing homes or in specialist palliative care institutions, while only 26% died at home in 2005 [13]. A similar pattern is seen in other European countries, as the place of death in Europe is most frequently hospital or nursing home [14]. Even in the UK, which has a well-developed and comprehensive national palliative care system, a study analyzing all cancer deaths between 1993 and 2010 showed that 48% died in a hospital and 16% in hospices, while 25% died at home [15]. Timely and continuous involvement of General Practitioners (GP), nurses and - when necessary - a Specialized Palliative Care Team (SPT) seems to have a positive impact on the likelihood of dying at home [16, 17]. Experience from the UK also showed that pronounced delay in the discharge from the hospital was a major obstacle to achieving the preferred place of palliative care and death [18].

In cancer care the availability of SPC seems to be a strong predictor for achieving home deaths [19‐22]. A prospective study demonstrated that agreement and understanding between patients and informal caregivers about patients’ preferred place of palliative care seems to be a crucial prerequisite for obtaining death at home [23]. Grande and Ewing found that this consensus resulted in a substantial likelihood that the patient died at his or her preferred place [23]. It is interesting to note that place of death can be a proxy for place of care. A systematic review from 2006 explored the factors influencing death at home [24]. Among the main factors strongly associated with death at home, patient’s preference for home death and home care were clearly expressed [24].

Integration and coordination between oncological treatment, SPC and standard care may be the best way to organize the palliative care for patients with cancer [25]. This approach could give patients the advantage of timely access to care at home and simultaneous improvement of symptom control and quality of life [25]. Brumley et al. conducted a randomized controlled trial of palliative care at home with terminally ill patients (late-stage patients with cancer, chronic obstructive pulmonary disease, and congestive heart failure), which reported a significant increase in satisfaction with care 30 and 90 days after enrollment [26]. More patients died at home (71%) compared to those receiving standard care (51%) and the intervention group was less likely to visit emergency rooms or be admitted to hospitals (36% compared to 59% in the control group), resulting in significantly lower costs [26].

Another advantage of SPC at home is the possibility to support bereaved relatives and caregivers [27]. In most cases, the grief process is uncomplicated, however, for up to 15% of bereaved relatives grief may develop into a psycho-pathological condition [28]. The World Health Organization’s (WHO) definition of palliative care emphasizes that the informal caregivers’ health and needs should also be assessed and supported in palliative care [29]. Informal caregivers of patients with advanced cancer can experience deterioration of their own health and mental well-being [30]. Furthermore, caregivers’ wishes regarding the place of death for their loved ones and their perception of the social support they received seem to be significantly associated with place of death [31].

We also considered measures of telomere length in caregivers of cancer patients as a measure for an effect of the intervention. The pathophysiological consequences of caregiving have not been fully elucidated and several studies indicate that caregivers’ stress and strain may be associated with shorter telomere length, a marker of cellular aging. A study of 338 caregivers in the 2008–2010 Survey of the Health of Wisconsin observed significantly shorter telomere length associated with number of hours per week of caregiving, caring for a younger individual, and more strain. Caregivers with discordant levels of stress and strain (i.e., low perceived stress/high strain) compared with low stress/low strain had significantly shorter telomeres corresponding to approximately 10–15 additional years of aging [32].

Thus, the DOMUS study protocol will describe an investigation of accelerated transition from oncological treatment to SPC at home for patients with incurable cancer in order to support patients and their informal caregivers to reach and stay in their preferred place of care and death.

The DOMUS trial is a comprehensive RCT in incurable cancer patients – to our knowledge the first of its kind - including outcomes from the individual patient and closest relative, as well as healthcare research of economy and organization. The primary goal of this trial is to ensure accelerated transition from hospital to SPC at home, so patients with incurable cancer can obtain timely transferal to and prolonged residence in their own homes [11]. The model is based on already existing resources, which are organized in a fixed sequence – a “fast-track lane” - with the addition of a manualized psychological intervention. The psychological intervention aims to support patients and caregivers jointly, as coping with severe illnesses depends, not only on the individual, but the dyad [47]. The effect of accelerated transition to a SPT enriched with a psychologist intervention will hopefully provide further knowledge of the needs of patients and caregivers as well as the costs and the expenses associated with the intervention. Finally, our study will, due to the transparency (Ref: Clinicaltrials.gov Identifier: NCT01885637) and the present paucity of comprehensive RCTs regarding clinical, organizational and health economical aspects of SPC, be valuable for decision-making in our region as well as in countries with comparable healthcare systems, and hopefully also be a source of inspiration for other healthcare systems [31, 48]. In developing the DOMUS trial, the authors have discussed several issues, which may raise criticism and pose challenges to feasibility and influence outcomes. One of them is obtaining agreement between patients and relatives about place of care. In our population, we have no data on the degree of agreement, which of course may be highly dependent on the quality and extent of information. In the DOMUS trial, this information is given by trained research nurses and based on an information manual regarding SPC at home. In a retrospective study, 80% of the patients and relatives agreed on the preferred place of death, and 20% of the relatives changed their minds (in 51% of these cases the preference moved from home to another setting) [49]. However, in this study the patients’ preferred place of death was given by the relatives after the deaths of their loved ones, and therefore the “true” proportion of agreement is uncertain [49]. Based on the retrospective data and our clinical experience, we anticipate that thorough and proper information about SPC at home will create agreement in the majority of cases.

Another issue of discussion in the DOMUS trial has been to define the inclusion criteria. Cancer patients who are eligible for SPT can be defined in many ways depending on the purpose of the study or clinical outcomes. A RCT by Temel et al. demonstrated that patients with newly diagnosed metastatic lung cancer benefitted from referral to a SPT, as these patients achieved better quality of life, were less depressed and lived longer than patients in a control group who received standard therapy [48]. Thus, the Temel study was engaged in early intervention of SPC for a specific cancer diagnosis [48], whereas our study is engaged in defining patients with different cancer diagnoses treated at a comprehensive cancer center in need of SPC at home. Therefore, in addition to the expressed wish (and agreement between patient and closest relative) to be cared for at home, we have selected the inclusion criteria “incurable cancer with limited or no antineoplastic treatment left” (List of Inclusion and exclusion criteria of the DOMUS study). Further, we have characterized the meaning of “incurable cancer with limited or no antineoplastic treatment left” for all involved diagnoses (Table 1). Hence, we have sought to define a palliative patient population suitable for and in need of SPC at home, which of course can be adapted to other diagnoses as well. By defining limited treatment options, we have established a set of criteria that are already an integrated part of oncological treatment. With these criteria, we may in the future enable clinicians to proactively identify patients in the oncological treatment trajectory, who may benefit from SPC. In the initial phase of the inclusion of patients ECOG performance status 2–4 was an inclusion criterion. However, after a year of inclusion only 66 patients were enrolled. In order to speed up recruitment of patients as well as attempting to study earlier SPC [29, 48] we have decided to remove the criteria (ECOG performance status 2–4). Further, by deleting the inclusion criteria it will be possible to investigate the difference effect of SPC in low and high ECOG performance status patients. The changes will be reported to clinicaltrial.gov.

The planned intervention is complex, including several sequential elements, and therefore it will not be possible to evaluate single elements of this multimodal trajectory intervention. The accelerated transition from oncological treatment requires a flexible primary care setting and a SPT ready to take care of the patient at home within five days of enrolment in the trial. The SPTs in the Capital Region of Denmark have their own individual referral guidelines and operate in less well-defined local areas. To ensure an equal distribution of patients to the different SPTs, the DOMUS protocol allocates patients to relevant SPTs according to uniformed referral guidelines and geographical based allocation. The geographical distribution of adequate SPC and the collaboration between SPTs, GPs, and district nurses is a rather simple prerequisite for the delivery of good palliative care. In addition, this issue may play a significant role even in countries with well-developed palliative care. In the UK with a comprehensive coverage of palliative care obtainable across the country, there seems to remain a lot of inequity, including that relating to geography, diagnosis, age and ethnicity [50]. In the DOMUS trial we will, in addition to the introduction of uniformed referral guidelines and geographical based allocation, further investigate these issues by adding qualitative interviews with patients, informal caregivers and healthcare professionals.

Currently a psychological intervention is not included in the standard SPT in Denmark, although it is recommended that a SPT consist of doctors, nurses, and one or more other medical professionals [14, 51]. In five out of nine SPTs in the Capital Region a psychologist is already part of the hospice/palliative care unit team, but as the capacity is limited the psychologists are only used for in-patients except in two palliative care units, where they can participate in SPC at home [32]. However, as all SPTs of the region have agreed to participate in the DOMUS trial, the standardized manualized psychologist intervention is applied to all patients and relatives allocated to the intervention group. Thus, if the multimodal trajectory intervention enriched with a targeted psychologist intervention proves to be successful it may inspire the future model for SPC.

The intervention proposed in the DOMUS trial requires a consistent and intensified collaboration between healthcare professionals in the hospital, the primary healthcare sector and the SPTs in order to give the patients the best possible care at home. The DOMUS study is primarily important, because it can show whether the intervention can improve the treatment of palliative patients and provide a model for how the SPC should be organized in the community. It is essential to find out whether place of care and death, longer survival and healthcare benefits are associated with the intervention. As the organizational and financial consequences of the model will also be investigated, there is a direct basis on which decisions can be taken regarding the organization of future palliative care. In addition to national importance of the study it has great international relevance, since high quality evidence from RCTs is sparse in palliative care, and no RCTs with an accelerated transition from oncological treatment to continuing SPC at home in patients with incurable cancer have previously been published.